Upregulation of Fas-signalling molecules in lung epithelial cells from patients with idiopathic pulmonary fibrosis
2001
The caspase cascade is an executioner of apoptosis, mediated by Fas. Fas-associating
protein with death domain (FADD) interacts with Fas and initiates
apoptosis through activating caspase-8. It has previously been demonstrated
that the Fas-Fas ligand pathway may be involved in the pathophysiology
of idiopathic pulmonary fibrosis (IPF). The aim of this study was
to investigate Fas-signalling molecules in epithelial cells in IPF. The immunohistochemistry for FADD and caspase-1 and -3 and
terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate
nick endlabelling (TUNEL) methods were performed in lung tissues
from 10 patients with IPF obtained by thoracoscopic biopsy and in seven normal
lung parenchyma specimens. The induction of caspases expression and activation
by Fas-ligation on lung epithelial cell line A549 was also investigated. The immunoreactivity grade for FADD and caspase-1 and -3,
and positive signals for TUNEL were significantly increased in epithelial
cells of IPF compared with controls. Fas-ligation induced upregulation
of caspase-1 and -3 expression in the nucleus and cytoplasm
in A549 cells. Procaspase-1, -3, and -8 were activated
in apoptotic cells, but not in viable cells. Although direct measurement of the caspase activity in lung epithelial
cells of idiopathic pulmonary fibrosis could not be made, these results suggest
that the Fas-signalling pathway is upregulated in lung epithelial cells
of idiopathic pulmonary fibrosis.
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